Pharmacological research最新文献

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Correspondence: Improved glycemic and weight control with Dulaglutide addition in SGLT2 inhibitor treated obese type 2 diabetic patients at high cardiovascular risk in a real-world setting. The AWARE-2 study

IF 9.1 2区医学 Q1 PHARMACOLOGY & PHARMACY

Pharmacological research

Pub Date : 2025-03-01 DOI: 10.1016/j.phrs.2025.107639

Chang-Yuan Hsu, Che-Wei Chang, Su-Boon Yong, Chin-Yuan Yii

引用次数: 0

Corrigendum to “Ectopic expression of NKG7 enhances CAR-T function and improves the therapeutic efficacy in liquid and solid tumors” [Pharmacol. Res. 210 (2024) 107506] 更正："异位表达 NKG7 可增强 CAR-T 功能并提高液体和固体肿瘤的疗效" [Pharmacol. Res. 210 (2024) 107506]。

IF 9.1 2区医学 Q1 PHARMACOLOGY & PHARMACY

Pharmacological research

Pub Date : 2025-03-01 DOI: 10.1016/j.phrs.2025.107669

Yuxin Chen , Meng Wang , Shuxin Huang , Lulu Han , Ying Cai , Xiaodi Xu , Shuwen Sun , Zhaokai Chen , Junze Chen , Jiatian Yu , Hongwei Du , Huizhong Li , Junnian Zheng , Bo Ma , Gang Wang

引用次数: 0

Reply to the letter comment of Su Boon Yong MD, PhD and colleagues to: Improved glycemic and weight control with Dulaglutide addition in SGLT2 inhibitor treated obese type 2 diabetic patients at high cardiovascular risk in a real-world setting. The AWARE− 2 study

IF 9.1 2区医学 Q1 PHARMACOLOGY & PHARMACY

Pharmacological research

Pub Date : 2025-03-01 DOI: 10.1016/j.phrs.2025.107640

Cesare Berra, Roberto Manfrini, Francesco Bifari, Elisa Cipponeri, Renata Ghelardi, Lucia Centofanti, Umberto Mortola, Elena Lunati, Loredana Bucciarelli, Vincenzo Cimino, Franco Folli

引用次数: 0

A theranostic photosensitizer-conjugated albumin co-loading with resiquimod for cancer-targeted imaging and robust photo-immunotherapy: Critical considerations from bench to bedside

IF 9.1 2区医学 Q1 PHARMACOLOGY & PHARMACY

Pharmacological research

Pub Date : 2025-02-26 DOI: 10.1016/j.phrs.2025.107673

Peng Sheng, Shi Zhou

引用次数: 0

USP19 deficiency enhances T-cell-mediated antitumor immunity by promoting PD-L1 degradation in colorectal cancer

IF 9.1 2区医学 Q1 PHARMACOLOGY & PHARMACY

Pharmacological research

Pub Date : 2025-02-26 DOI: 10.1016/j.phrs.2025.107668

Feng Shi , Guang-Jing Li , Yi Liu , Hai-Meng Zhou , Yue Zhang , Si-Yi Wei , Bo-Jun Zan , Meng Gao , Fei-Shan Chen , Bo-Xin Li , Bai-Qi Wang , Ming-You Dong , Run-Lei Du , Xiao-Dong Zhang

Colorectal cancer (CRC) is characterized by a highly immunosuppressive tumor microenvironment, which limits the effectiveness of current immunotherapies. Identifying strategies to overcome this resistance is critical for improving treatment outcomes. In this study, we discovered that USP19 plays a pivotal role in regulating T-cell-mediated antitumor immunity through a CRISPR/Cas9 sgRNA library screen and co-culture assays with activated T cells. We demonstrated that USP19 deficiency significantly enhances the susceptibility to T cell-mediated cytotoxicity in CRC cells, organoids, and mouse models. Transcriptomic sequencing (RNA-seq) revealed activation of the PD-1 pathway in tumor with USP19-deficiency cells. Mechanistic investigations revealed that USP19 directly stabilizes PD-L1 by binding to its intracellular domain and preventing its degradation via K48-linked ubiquitination and proteasomal pathways. Clinically, USP19 expression was found to be significantly elevated in CRC tissues and was positively associated with PD-L1 levels, advanced tumor grade, poor differentiation, and TP53 mutations, highlighting its potential as a biomarker for aggressive CRC. Importantly, in vivo experiments demonstrated that targeting USP19, in combination with αPD-L1 therapy, synergistically suppressed CRC progression. This combination not only reduced PD-L1 levels but also enhanced CD8⁺ T-cell activation and GzmB infiltration, resulting in robust antitumor effects. These findings establish USP19 as a key driver of immune evasion in CRC and suggest that targeting USP19 could enhance the efficacy of immunotherapy, providing a promising new avenue for CRC treatment.

{"title":"USP19 deficiency enhances T-cell-mediated antitumor immunity by promoting PD-L1 degradation in colorectal cancer","authors":"Feng Shi , Guang-Jing Li , Yi Liu , Hai-Meng Zhou , Yue Zhang , Si-Yi Wei , Bo-Jun Zan , Meng Gao , Fei-Shan Chen , Bo-Xin Li , Bai-Qi Wang , Ming-You Dong , Run-Lei Du , Xiao-Dong Zhang","doi":"10.1016/j.phrs.2025.107668","DOIUrl":"10.1016/j.phrs.2025.107668","url":null,"abstract":"<div><div>Colorectal cancer (CRC) is characterized by a highly immunosuppressive tumor microenvironment, which limits the effectiveness of current immunotherapies. Identifying strategies to overcome this resistance is critical for improving treatment outcomes. In this study, we discovered that USP19 plays a pivotal role in regulating T-cell-mediated antitumor immunity through a CRISPR/Cas9 sgRNA library screen and co-culture assays with activated T cells. We demonstrated that USP19 deficiency significantly enhances the susceptibility to T cell-mediated cytotoxicity in CRC cells, organoids, and mouse models. Transcriptomic sequencing (RNA-seq) revealed activation of the PD-1 pathway in tumor with USP19-deficiency cells. Mechanistic investigations revealed that USP19 directly stabilizes PD-L1 by binding to its intracellular domain and preventing its degradation via K48-linked ubiquitination and proteasomal pathways. Clinically, USP19 expression was found to be significantly elevated in CRC tissues and was positively associated with PD-L1 levels, advanced tumor grade, poor differentiation, and TP53 mutations, highlighting its potential as a biomarker for aggressive CRC. Importantly, in vivo experiments demonstrated that targeting USP19, in combination with αPD-L1 therapy, synergistically suppressed CRC progression. This combination not only reduced PD-L1 levels but also enhanced CD8<sup>+</sup> T-cell activation and GzmB infiltration, resulting in robust antitumor effects. These findings establish USP19 as a key driver of immune evasion in CRC and suggest that targeting USP19 could enhance the efficacy of immunotherapy, providing a promising new avenue for CRC treatment.</div></div>","PeriodicalId":19918,"journal":{"name":"Pharmacological research","volume":"214 ","pages":"Article 107668"},"PeriodicalIF":9.1,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143512745","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The dynamic role of ferroptosis in cancer immunoediting: Implications for immunotherapy 铁突变在癌症免疫编辑中的动态作用：对免疫疗法的影响

IF 9.1 2区医学 Q1 PHARMACOLOGY & PHARMACY

Pharmacological research

Pub Date : 2025-02-26 DOI: 10.1016/j.phrs.2025.107674

Jiarui Lan , Dan Cai , Shuang Gou , Yulin Bai , Huaqing Lei , Yan Li , Yu Chen , Yueshui Zhao , Jing Shen , Xu Wu , Mingxing Li , Meijuan Chen , Xiaobing Li , Yuhong Sun , Li Gu , Wanping Li , Fang Wang , Chi Hin Cho , Yan Zhang , Xin Zheng , Fukuan Du

Currently, cancer immunotherapy strategies are primarily formulated based on the patient's present condition, representing a "static" treatment approach. However, cancer progression is inherently "dynamic," as the immune environment is not fixed but undergoes continuous changes. This dynamism is characterized by the ongoing interactions between tumor cells and immune cells, which ultimately lead to alterations in the tumor immune microenvironment. This process can be effectively elucidated by the concept of cancer immunoediting, which divides tumor development into three phases: "elimination," "equilibrium," and "escape." Consequently, adjusting immunotherapy regimens based on these distinct phases may enhance patient survival and improve prognosis. Targeting ferroptosis is an emerging area in cancer immunotherapy, and our findings reveal that the antioxidant systems associated with ferroptosis possess dual roles, functioning differently across the three phases of cancer immunoediting. Therefore, this review delve into the dual role of the ferroptosis antioxidant system in tumor development and progression. It also propose immunotherapy strategies targeting ferroptosis at different stages, ultimately aiming to illuminate the significant implications of targeting ferroptosis at various phases for cancer immunotherapy.

目前，癌症免疫疗法策略主要是根据患者目前的病情制定的，是一种 "静态 "的治疗方法。然而，癌症的进展本质上是 "动态 "的，因为免疫环境不是固定不变的，而是在不断变化。这种动态性的特点是肿瘤细胞和免疫细胞之间不断发生相互作用，最终导致肿瘤免疫微环境的改变。癌症免疫编辑的概念可以有效地阐明这一过程，它将肿瘤的发展分为三个阶段："消除"、"平衡 "和 "逃逸"。因此，根据这些不同阶段调整免疫疗法方案可提高患者生存率并改善预后。我们的研究结果表明，与铁氧化相关的抗氧化系统具有双重作用，在癌症免疫诱导的三个阶段中发挥着不同的功能。因此，这篇综述深入探讨了铁氧化抗氧化系统在肿瘤发生和发展过程中的双重作用。它还提出了针对不同阶段的铁氧化的免疫治疗策略，最终旨在阐明针对不同阶段的铁氧化对癌症免疫治疗的重要意义。

{"title":"The dynamic role of ferroptosis in cancer immunoediting: Implications for immunotherapy","authors":"Jiarui Lan , Dan Cai , Shuang Gou , Yulin Bai , Huaqing Lei , Yan Li , Yu Chen , Yueshui Zhao , Jing Shen , Xu Wu , Mingxing Li , Meijuan Chen , Xiaobing Li , Yuhong Sun , Li Gu , Wanping Li , Fang Wang , Chi Hin Cho , Yan Zhang , Xin Zheng , Fukuan Du","doi":"10.1016/j.phrs.2025.107674","DOIUrl":"10.1016/j.phrs.2025.107674","url":null,"abstract":"<div><div>Currently, cancer immunotherapy strategies are primarily formulated based on the patient's present condition, representing a \"static\" treatment approach. However, cancer progression is inherently \"dynamic,\" as the immune environment is not fixed but undergoes continuous changes. This dynamism is characterized by the ongoing interactions between tumor cells and immune cells, which ultimately lead to alterations in the tumor immune microenvironment. This process can be effectively elucidated by the concept of cancer immunoediting, which divides tumor development into three phases: \"elimination,\" \"equilibrium,\" and \"escape.\" Consequently, adjusting immunotherapy regimens based on these distinct phases may enhance patient survival and improve prognosis. Targeting ferroptosis is an emerging area in cancer immunotherapy, and our findings reveal that the antioxidant systems associated with ferroptosis possess dual roles, functioning differently across the three phases of cancer immunoediting. Therefore, this review delve into the dual role of the ferroptosis antioxidant system in tumor development and progression. It also propose immunotherapy strategies targeting ferroptosis at different stages, ultimately aiming to illuminate the significant implications of targeting ferroptosis at various phases for cancer immunotherapy.</div></div>","PeriodicalId":19918,"journal":{"name":"Pharmacological research","volume":"214 ","pages":"Article 107674"},"PeriodicalIF":9.1,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143527523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cardiac fibroblast-derived mitochondria-enriched sEVs regulate tissue inflammation and ventricular remodeling post-myocardial infarction through NLRP3 pathway

IF 9.1 2区医学 Q1 PHARMACOLOGY & PHARMACY

Pharmacological research

Pub Date : 2025-02-25 DOI: 10.1016/j.phrs.2025.107676

Yuanyuan Zhao , Ya Hu , Yifei Wang , Hao Qian , Chenxu Zhu , Hongjian Dong , Chunshu Hao , Yao Zhang , Zhenjun Ji , Xinxin Li , Yue Chen , Rongfeng Xu , Jie Jiang , Hailong Cao , Genshan Ma , Lijuan Chen

Resident cardiac fibroblasts (CFs) play crucial roles in sensing injury signals and regulating inflammatory responses post-myocardial infarction (MI). Damaged mitochondria can be transferred extracellularly via various mechanisms, including extracellular vesicles (EVs). In this study, we aimed to investigate whether CFs could transfer damaged mitochondrial components via small EVs (sEVs) and elucidate their role in regulating inflammatory responses post-MI. Left anterior descending coronary artery ligation was performed in mice. Mitochondrial components in sEVs were detected using nanoflow cytometry. Differential protein expression in sEVs from normoxia and normoglycemia CFs (CFs-Nor-sEVs) and CFs post oxygen-glucose deprivation (CFs-OGD-sEVs) was identified using label-free proteomics. CFs-sEVs were co-cultured with mouse bone marrow-derived macrophages (BMDMs) to assess macrophage inflammatory responses. Effects of intramyocardial injection of CFs-sEVs were assessed in MI mice in the absence or presence of NLRP3 inhibitor CY-09. Results demonstrated that mitochondrial components were detected in CFs-derived sEVs post-MI. Damaged mitochondrial components were enriched in CFs-OGD-sEVs (CFs-mt-sEVs), which promoted pro-inflammatory phenotype activation of BMDMs in vitro. Myocardial injection of CFs-mt-sEVs enhanced tissue inflammation, aggravated cardiac dysfunction, and exacerbated maladaptive ventricular remodeling post-MI in vivo. Mechanistically, above effects were achieved via activation of NLRP3 and above effects could be reversed by NLRP3 inhibitor CY-09. This study indicates that CFs could transfer damaged mitochondrial components via the sEVs post-MI, promote macrophage inflammatory activation and exacerbate maladaptive ventricular remodeling post MI by activating NLRP3. Our findings highlight the potential therapeutic effects of inhibiting CFs-mt-sEVs and NLRP3 to improve cardiac function and attenuate ventricular remodeling post-MI.

{"title":"Cardiac fibroblast-derived mitochondria-enriched sEVs regulate tissue inflammation and ventricular remodeling post-myocardial infarction through NLRP3 pathway","authors":"Yuanyuan Zhao , Ya Hu , Yifei Wang , Hao Qian , Chenxu Zhu , Hongjian Dong , Chunshu Hao , Yao Zhang , Zhenjun Ji , Xinxin Li , Yue Chen , Rongfeng Xu , Jie Jiang , Hailong Cao , Genshan Ma , Lijuan Chen","doi":"10.1016/j.phrs.2025.107676","DOIUrl":"10.1016/j.phrs.2025.107676","url":null,"abstract":"<div><div>Resident cardiac fibroblasts (CFs) play crucial roles in sensing injury signals and regulating inflammatory responses post-myocardial infarction (MI). Damaged mitochondria can be transferred extracellularly via various mechanisms, including extracellular vesicles (EVs). In this study, we aimed to investigate whether CFs could transfer damaged mitochondrial components via small EVs (sEVs) and elucidate their role in regulating inflammatory responses post-MI. Left anterior descending coronary artery ligation was performed in mice. Mitochondrial components in sEVs were detected using nanoflow cytometry. Differential protein expression in sEVs from normoxia and normoglycemia CFs (CFs-Nor-sEVs) and CFs post oxygen-glucose deprivation (CFs-OGD-sEVs) was identified using label-free proteomics. CFs-sEVs were co-cultured with mouse bone marrow-derived macrophages (BMDMs) to assess macrophage inflammatory responses. Effects of intramyocardial injection of CFs-sEVs were assessed in MI mice in the absence or presence of NLRP3 inhibitor CY-09. Results demonstrated that mitochondrial components were detected in CFs-derived sEVs post-MI. Damaged mitochondrial components were enriched in CFs-OGD-sEVs (CFs-mt-sEVs), which promoted pro-inflammatory phenotype activation of BMDMs in vitro. Myocardial injection of CFs-mt-sEVs enhanced tissue inflammation, aggravated cardiac dysfunction, and exacerbated maladaptive ventricular remodeling post-MI in vivo. Mechanistically, above effects were achieved via activation of NLRP3 and above effects could be reversed by NLRP3 inhibitor CY-09. This study indicates that CFs could transfer damaged mitochondrial components via the sEVs post-MI, promote macrophage inflammatory activation and exacerbate maladaptive ventricular remodeling post MI by activating NLRP3. Our findings highlight the potential therapeutic effects of inhibiting CFs-mt-sEVs and NLRP3 to improve cardiac function and attenuate ventricular remodeling post-MI.</div></div>","PeriodicalId":19918,"journal":{"name":"Pharmacological research","volume":"214 ","pages":"Article 107676"},"PeriodicalIF":9.1,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143524106","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Plant-derived nanovesicles as novel nanotherapeutics for alleviating endothelial cell senescence-associated vascular remodeling induced by hypertension

IF 9.1 2区医学 Q1 PHARMACOLOGY & PHARMACY

Pharmacological research

Pub Date : 2025-02-25 DOI: 10.1016/j.phrs.2025.107675

Fengxia Lin , Luhua Xu , Qiuting He , Zetao Chen , Weiwei Zhang , Jin Tu , Yinzhi Song , Fanjia Zhong , Sheng Lin , Rongfeng Yang , Zhicong Zeng

Endothelial cell senescence contributes to vascular remodeling in hypertension, a condition that lacks specific clinical treatments. While plant-derived nanovesicles have shown anti-inflammatory properties that reduce endothelial inflammation, their role in endothelial cell senescence is less understood. Here, we isolated and purified nanovesicles from Semen Sinapis albae (SDNVs), a traditional Chinese medicine with antihypertensive properties, and evaluated their therapeutic effects on vascular remodeling in spontaneously hypertensive rats (SHRs) compared to nifedipine, a standard antihypertensive drug. SDNVs were as effective as nifedipine in reducing blood pressure and exceeded nifedipine in mitigating vascular wall thickening, collagen fiber disarray, and in decreasing senescence markers in aortic tissues. In vitro, SDNVs inhibited angiotensin II-induced senescence in human umbilical vein endothelial cells (HUVECs). miRNA and mRNA sequencing revealed that SDNVs downregulate CD38 expression through miR393a delivery, mediating their anti-senescence effects. Our results suggest that SDNVs significantly alleviate hypertension-associated vascular remodeling by targeting CD38 via miR393a, thus reducing endothelial cell senescence. Compared to conventional drugs like nifedipine, SDNVs offer a potentially more effective approach to vascular remodeling. These insights may guide the development of novel therapeutics for hypertension-induced vascular remodeling.

{"title":"Plant-derived nanovesicles as novel nanotherapeutics for alleviating endothelial cell senescence-associated vascular remodeling induced by hypertension","authors":"Fengxia Lin , Luhua Xu , Qiuting He , Zetao Chen , Weiwei Zhang , Jin Tu , Yinzhi Song , Fanjia Zhong , Sheng Lin , Rongfeng Yang , Zhicong Zeng","doi":"10.1016/j.phrs.2025.107675","DOIUrl":"10.1016/j.phrs.2025.107675","url":null,"abstract":"<div><div>Endothelial cell senescence contributes to vascular remodeling in hypertension, a condition that lacks specific clinical treatments. While plant-derived nanovesicles have shown anti-inflammatory properties that reduce endothelial inflammation, their role in endothelial cell senescence is less understood. Here, we isolated and purified nanovesicles from <em>Semen Sinapis albae</em> (SDNVs), a traditional Chinese medicine with antihypertensive properties, and evaluated their therapeutic effects on vascular remodeling in spontaneously hypertensive rats (SHRs) compared to nifedipine, a standard antihypertensive drug. SDNVs were as effective as nifedipine in reducing blood pressure and exceeded nifedipine in mitigating vascular wall thickening, collagen fiber disarray, and in decreasing senescence markers in aortic tissues. In <em>vitro</em>, SDNVs inhibited angiotensin II-induced senescence in human umbilical vein endothelial cells (HUVECs). miRNA and mRNA sequencing revealed that SDNVs downregulate CD38 expression through miR393a delivery, mediating their anti-senescence effects. Our results suggest that SDNVs significantly alleviate hypertension-associated vascular remodeling by targeting CD38 via miR393a, thus reducing endothelial cell senescence. Compared to conventional drugs like nifedipine, SDNVs offer a potentially more effective approach to vascular remodeling. These insights may guide the development of novel therapeutics for hypertension-induced vascular remodeling.</div></div>","PeriodicalId":19918,"journal":{"name":"Pharmacological research","volume":"214 ","pages":"Article 107675"},"PeriodicalIF":9.1,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143510426","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Gut microbiota-derived metabolites: Potential targets for cardiorenal syndrome

IF 9.1 2区医学 Q1 PHARMACOLOGY & PHARMACY

Pharmacological research

Pub Date : 2025-02-24 DOI: 10.1016/j.phrs.2025.107672

Yuchen Lai , Yujie Zhu , Xihui Zhang , Shifang Ding , Fang Wang , Jincen Hao , Zhaomeng Wang , Congqi Shi , Yongjin Xu , Lemin Zheng , Wei Huang

The characteristic of cardiorenal syndrome (CRS) is simultaneous damage to both the heart and kidneys. CRS has caused a heavy burden of mortality and incidence rates worldwide. The regulation of host microbiota metabolism that triggers heart and kidney damage is an emerging research field that promotes a new perspective on cardiovascular risk. We summarize current studies from bench to bedside of gut microbiota-derived metabolites to better understand CRS in the context of gut microbiota-derived metabolites. We focused on the involvement of gut microbiota-derived metabolites in the pathophysiology of CRS, including lipid and cholesterol metabolism disorders, coagulation abnormalities and platelet aggregation, oxidative stress, endothelial dysfunction, inflammation, mitochondrial damage and energy metabolism disorders, vascular calcification and renal fibrosis, as well as emerging therapeutic approaches targeting CRS metabolism in gut microbiota-derived metabolites which provides an innovative treatment approach for CRS to improve patient prognosis and overall quality of life.

{"title":"Gut microbiota-derived metabolites: Potential targets for cardiorenal syndrome","authors":"Yuchen Lai , Yujie Zhu , Xihui Zhang , Shifang Ding , Fang Wang , Jincen Hao , Zhaomeng Wang , Congqi Shi , Yongjin Xu , Lemin Zheng , Wei Huang","doi":"10.1016/j.phrs.2025.107672","DOIUrl":"10.1016/j.phrs.2025.107672","url":null,"abstract":"<div><div>The characteristic of cardiorenal syndrome (CRS) is simultaneous damage to both the heart and kidneys. CRS has caused a heavy burden of mortality and incidence rates worldwide. The regulation of host microbiota metabolism that triggers heart and kidney damage is an emerging research field that promotes a new perspective on cardiovascular risk. We summarize current studies from bench to bedside of gut microbiota-derived metabolites to better understand CRS in the context of gut microbiota-derived metabolites. We focused on the involvement of gut microbiota-derived metabolites in the pathophysiology of CRS, including lipid and cholesterol metabolism disorders, coagulation abnormalities and platelet aggregation, oxidative stress, endothelial dysfunction, inflammation, mitochondrial damage and energy metabolism disorders, vascular calcification and renal fibrosis, as well as emerging therapeutic approaches targeting CRS metabolism in gut microbiota-derived metabolites which provides an innovative treatment approach for CRS to improve patient prognosis and overall quality of life.</div></div>","PeriodicalId":19918,"journal":{"name":"Pharmacological research","volume":"214 ","pages":"Article 107672"},"PeriodicalIF":9.1,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143516277","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Knowledge of the genetics of human pain gained over the last decade from next-generation sequencing

IF 9.1 2区医学 Q1 PHARMACOLOGY & PHARMACY

Pharmacological research

Pub Date : 2025-02-21 DOI: 10.1016/j.phrs.2025.107667

Dario Kringel , Jörn Lötsch

Next-generation sequencing (NGS) technologies have revolutionized pain research by providing comprehensive insights into genetic variation across the genome. Recent studies have expanded the known spectrum of mutations in genes such as SCN9A and NTRK1, which are commonly mutated in hereditary sensory neuropathies. NGS has uncovered critical alternative splicing events and facilitated single-cell transcriptomics, revealing cellular heterogeneity within tissues. An NGS-based classifier predicted extremely high opioid requirements with 80 % accuracy, highlighting the importance of tailoring opioid therapy based on genetic profiles. Key genes such as GDF5, COL11A1, and TRPV1 have been linked to osteoarthritis risk and pain sensitivity, while HLA-DRB1, TNF, and P2X7 play critical roles in inflammation and pain modulation in rheumatoid arthritis. Innovative tools, such as an atlas of the somatosensory system in neuropathic pain, have been developed based on NGS data, focusing on the dorsal root and trigeminal ganglia. This approach allows the analysis of cellular changes during the development of chronic pain. In the study of rare variants, NGS outperforms single nucleotide variant candidate studies and classical genome-wide association approaches. The complex data generated by NGS enables integrated multi-omics approaches, allowing deeper exploration of the molecular and cellular basis of pain perception. In addition, the characterization of non-coding RNAs has opened new therapeutic avenues. NGS-based pain research faces challenges related to complex data analysis and interpretation of rare genetic variants with unknown biological functions. Nevertheless, NGS offers significant potential for improving personalized pain management and highlights the need for interdisciplinary collaboration to translate findings into clinical practice.

{"title":"Knowledge of the genetics of human pain gained over the last decade from next-generation sequencing","authors":"Dario Kringel , Jörn Lötsch","doi":"10.1016/j.phrs.2025.107667","DOIUrl":"10.1016/j.phrs.2025.107667","url":null,"abstract":"<div><div>Next-generation sequencing (NGS) technologies have revolutionized pain research by providing comprehensive insights into genetic variation across the genome. Recent studies have expanded the known spectrum of mutations in genes such as <em>SCN9A</em> and <em>NTRK1</em>, which are commonly mutated in hereditary sensory neuropathies. NGS has uncovered critical alternative splicing events and facilitated single-cell transcriptomics, revealing cellular heterogeneity within tissues. An NGS-based classifier predicted extremely high opioid requirements with 80 % accuracy, highlighting the importance of tailoring opioid therapy based on genetic profiles. Key genes such as <em>GDF5</em>, <em>COL11A1</em>, and <em>TRPV1</em> have been linked to osteoarthritis risk and pain sensitivity, while <em>HLA-DRB1</em>, <em>TNF</em>, and <em>P2X7</em> play critical roles in inflammation and pain modulation in rheumatoid arthritis. Innovative tools, such as an atlas of the somatosensory system in neuropathic pain, have been developed based on NGS data, focusing on the dorsal root and trigeminal ganglia. This approach allows the analysis of cellular changes during the development of chronic pain. In the study of rare variants, NGS outperforms single nucleotide variant candidate studies and classical genome-wide association approaches. The complex data generated by NGS enables integrated multi-omics approaches, allowing deeper exploration of the molecular and cellular basis of pain perception. In addition, the characterization of non-coding RNAs has opened new therapeutic avenues. NGS-based pain research faces challenges related to complex data analysis and interpretation of rare genetic variants with unknown biological functions. Nevertheless, NGS offers significant potential for improving personalized pain management and highlights the need for interdisciplinary collaboration to translate findings into clinical practice.</div></div>","PeriodicalId":19918,"journal":{"name":"Pharmacological research","volume":"214 ","pages":"Article 107667"},"PeriodicalIF":9.1,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143483604","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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Pharmacological research

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